Robo1-Fc fusion protein and use thereof for treating tumours

Abstract

The present invention relates to a Robo1-Fc recombinant protein and to the use thereof for treating diseases in which a Slit protein is overexpressed, in particular cancer. The invention also relates to a composition including such a recombinant protein. Another aspect of the invention involves using a Robo1-Fc molecule as a diagnostic tool for detecting the overexpression of a molecule belonging to the Slit family in a patient.

We claim: 
     
       1. A homogeneous composition of Robo-Fc recombinant protein comprising the extracellular region of a Robo1 protein, a linker and an immunoglobulin Fc domain,
 wherein said extracellular region of the Robo1 protein consists of the Ig1 and Ig2 immunoglobulin domains corresponding to amino acids 22-220 of SEQ ID NO: 2, 
 wherein the immunoglobulin Fc domain is from human immunoglobulin G4 and comprises S241P and L248E mutations (Kabat numbering), and wherein the lysine located in the C-terminal position is absent. 
 
     
     
       2. The homogeneous composition of Robo-Fc recombinant protein according to  claim 1 , wherein the sequence has at least 80% identity with the sequence of SEQ ID NO: 4, SEQ ID NO: 6 or SEQ ID NO: 24. 
     
     
       3. A pharmaceutical composition comprising the homogeneous composition of Robo-Fc recombinant protein of  claim 1 . 
     
     
       4. A method for treating a cancer associated with overexpression of a protein of the Slit family comprising administering to a subject in need thereof the pharmaceutical composition of  claim 3 . 
     
     
       5. The method of  claim 4 , wherein the cancer is lung cancer or lung metastases. 
     
     
       6. The pharmaceutical composition according to  claim 3  further comprising at least one excipient. 
     
     
       7. A method for detecting overexpression of a molecule of the Slit family in a patient comprising contacting a biological sample from the patient with the homogeneous composition of Robo-Fc recombinant protein of  claim 1 . 
     
     
       8. The homogeneous composition of Robo-Fc recombinant protein according to  claim 1 , which is produced by transfection of expression plasmid encoding a protein having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6 or SEQ ID NO: 24 into CHO cell, recovery in culture supernatant and purification. 
     
     
       9. The homogeneous composition of Robo-Fc recombinant protein according to  claim 1 , wherein the Robo-Fc recombinant protein consists of amino acids 22 to 454 of SEQ ID NO: 4. 
     
     
       10. The homogeneous composition of Robo-Fc recombinant protein according to  claim 1 , wherein the Robo-Fc recombinant protein consists of amino acids 22 to 453 of SEQ ID NO: 6. 
     
     
       11. The homogeneous composition of Robo-Fc recombinant protein according to  claim 1 , wherein the Robo-Fc recombinant protein consists of amino acids 21 to 453 of SEQ ID NO: 24.